BACKGROUND: Cisplatin is a cytotoxic drug with radiosensitizing effect. In this study a physical drug delivery system, electroporation, was used to facilitate cisplatin delivery into the cells and tumors with the aim of increasing radiation response. MATERIALS AND METHODS: LPB murine sarcoma cells and tumors were treated either by cisplatin, electroporation or ionizing radiation, and combinations of these. In vitro radiation response was determined by colony forming assay while in vivo treatment effectiveness was determined by local tumor control (TCD50). Platinum accumulation in tumors by atomic absorption spectrometry and tumor perfusion changes by Patent blue staining were determined to elucidate some underlying antitumor mechanisms. RESULTS: Exposure of cells in vitro to a combination of cisplatin and electroporation followed by irradiation increased the radiosensitizing effect of cisplatin. Also, the tumor radiocurability of this combined treatment was significantly enhanced, compared to irradiated tumors (enhancement factor; EF = 1.6) and to tumors treated with cisplatin and irradiation (EF = 1.4). Application of electric pulses to the tumors resulted in increased and prolonged accumulation of cisplatin and reduced tumor perfusion. CONCLUSION: This study demonstrated that electroporation of cells and tumors increases the radiosensitizing effect of cisplatin, and that the predominant underlying mechanism is increased platinum delivery into the tumors due to the electroporation.
BACKGROUND:Cisplatin is a cytotoxic drug with radiosensitizing effect. In this study a physical drug delivery system, electroporation, was used to facilitate cisplatin delivery into the cells and tumors with the aim of increasing radiation response. MATERIALS AND METHODS: LPB murinesarcoma cells and tumors were treated either by cisplatin, electroporation or ionizing radiation, and combinations of these. In vitro radiation response was determined by colony forming assay while in vivo treatment effectiveness was determined by local tumor control (TCD50). Platinum accumulation in tumors by atomic absorption spectrometry and tumor perfusion changes by Patent blue staining were determined to elucidate some underlying antitumor mechanisms. RESULTS: Exposure of cells in vitro to a combination of cisplatin and electroporation followed by irradiation increased the radiosensitizing effect of cisplatin. Also, the tumor radiocurability of this combined treatment was significantly enhanced, compared to irradiated tumors (enhancement factor; EF = 1.6) and to tumors treated with cisplatin and irradiation (EF = 1.4). Application of electric pulses to the tumors resulted in increased and prolonged accumulation of cisplatin and reduced tumor perfusion. CONCLUSION: This study demonstrated that electroporation of cells and tumors increases the radiosensitizing effect of cisplatin, and that the predominant underlying mechanism is increased platinum delivery into the tumors due to the electroporation.